1. Histology Anatomy & Physiology Diseases
Parathyroid Glands
Histology
Anatomy & Physiology
Diseases
faculty.orangecoastcollege.edu/.../BIOL226Lec08_%20Thyroid_Para.ppt
mssurg.net/Presentations/Parathyroid%20Glands%20-%20SNguyen.ppt 

2. Histology 50/50 parenchymal cells, stromal fat
Composed mostly of chief cells and oxyphil cells within adipose stroma (fat)
Oxyphil cells: derived from chief cells and increase as one ages
Both types make Parathyroid hormone

3. Anatomy
Superior glands usually imbedded in fat on posterior surface of middle or upper portion of thyroid lobe
Inferior glands near the lower part of thyroid gland
Most of blood supply from branches of inferior thyroid artery, although branches from superior thyroid supply at least 20% of upper glands.
Glands drain ipsillaterally by superior, middle, and inferior thyroid veins.

4. Parathyroid

5. Parathyroid Glands (posterior view of thyroid)
Parathyroid Glands are located on the posterior aspect of the thyroid; sometimes the tissue is embedded within thyroid tissue.

6. Parathyroid

7. Anatomy & Physiology
Usually four – two on each side (2-8 is normal) Parathyroid glands
1. Yellow-brown
2. oval or lentiform structures
3. weigh ~ 50 mg each
4. Measure 3-10 mm x 2-6 mm x 1-4 mm
Lie on the posterior surface of thyroid
May be embedded within thyroid gland
Regulate calcium/phosphate levels
Required for life

8. Parathyroid Hormone
Synthesized in chief cells as large precursor – pre-proparathyroid hormone
Cleaved intracellularly into proparathyroid hormone then to final 84 AA PTH
PTH then metabolized by liver into hormonally active N-term and inactive C-term

9. Calcium Homeostasis
The parathyroid cells rely on a G-protein-coupled membrane receptor designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels
PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, and hypomagnesemia.

10. Calcium Homeostasis
PTH is synthesized in the parathyroid gland as a precursor hormone,preproparathyroid hormone, which is cleaved first to proparathyroid hormone and then to the final 84-amino-acid PTH.
Secreted PTH has a half-life of 2 to 4 minutes. In the liver, PTH is metabolized into the active N-terminal component and the relatively inactive C-terminal fraction

11. Calcium homeostasis
The calcium-sensing receptor (CASR) senses fluctuations in the concentration of extracellular calcium.
Increased PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption.
PTH also stimulates renal 1- Hydroxylase activity, leading to an increase in 1,25-dihydroxy vitamin D, which also exerts a negative feedback on PTH secretion

12. Calcium homeostasis
PTH functions to regulate calcium levels via its actions on three target organs, the bone, kidney, and gut.
PTH increases the resorption of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation.

13. Calcium homeostasis
At the kidney, PTH acts to limit calcium excretion at the distal convoluted tubule via an active transport mechanism.
PTH also inhibits phosphate reabsorption (at the Proximal convoluted tubule) and bicarbonate reabsorption.
PTH and hypophosphatemia also enhance 1-hydroxylation of 25-Hydroxyvitamin D, which is responsible for its indirect effect of increasing intestinal calcium absorption.
faculty.orangecoastcollege.edu/.../BIOL226Lec08_%20Thyroid_Para.ppt

14. Parathyroid Diseases Benign adenoma a. Relatively common
b. Usually results in hyperparathyroidism
Cancers are rare
a. Surgical removal gives > 90% cure rate

15. Parathyroid Diseases Hyperparathyroidism Primary Hyperparathyroidism:
a. Affects about 100,000 patients per year
Primary Hyperparathyroidism:
occurs in 0.1 to 0.3% of the general population and is more common in women (1:500) than in men (1:2000).
Normal feedback of Ca is disturbed, causing increased production of PTH (does not depend on calcium concentration)
Acts on bone, kidneys, small intestines

16. Primary Hyperparathyroidism
Epidemiology
25/100,000
50,000 new cases yearly
F > M
Incidence increases w/ age
Most in > 50 years old
Etiology
Unknown cause
Ionizing radiation exposure?

17. Hyperparathyroidism Symptoms
Kidney stones, painful bones, abdominal groans, psychic moans, and fatigue overtones
Kidney stones calcium phosphate and oxalate
Osteopenia, osteoporosis, and osteitis fibrosa cystica, is found in approximately 15% of patients with PHPT. Increased bone turnover can usually be determined by documenting an elevated blood alkaline phosphatase level.
Peptic ulcer disease, pancreatitis
Psychiatric manifestations such as florid psychosis, obtubdation, coma, depression, anxiety, fatigue

18. Hyperparathyroidism (cont.)
Secondary Hyperparathyroidism
Defect in mineral homeostasis leading to a compensatory increase in parathyroid gland function
Tertiary Hyperparathyroidism
After prolonged over-compensatory stimulation, hyperplastic gland develops autonomous function

19. Hyperparathyroidism
Hypercalcemia can be from other sources. Intact PTH measurement and elevated PTH level very sensitive for hyperparathyroidism

20. Hypercalcemia – Etimology
Hyperparathyroidism (most common)
Malignancy (most common in hospitalized)
Lytic metastases to bone
PTHrP producer
Sarcoidosis / granulomatous disease
Hyperthyroidism
Familial hypocalciuric hypercalcemia

21. Renal Complications Generally the most severe clinical manifestations
Calcium phosphate or Calcium oxalate
Severe renal damage
Hypertension secondary to renal impairment

22. Bone Disease Osteitis fibrosa cystica
Generalized skeletal demineralization due to an increased rate of bone destruction resulting from hyperparathyroidism
In early descriptions of disease, many had severe bone disease (50-90%), but now 5-15%
Subperiosteal resorption – pathognomonic of hyperparathyroidism

23. Generalized skeletal demineralization due to an increased rate of bone destruction resulting from hyperparathyroidism

24. Gastrointestinal Manifestations
Peptic Ulcer disease
Pancreatitis
Cholelithiasis – 25-35%

25. Emotional Disturbances
Hypercalcemia of any cause – assoc w/ neurologic or psychiatric disturbances
Depression, anxiety, psychosis, coma
Severe disturbances not usually correctable by parathyroidectomy

26. Articular and Soft Tissue
Chondrocalcinosis and Pseudogout 3-7%
Deposits of Calcium pyrophosphate in articular cartilages and menisci
Vascular and Cardiac calcifications

27. Neuromuscular complications
Muscular weakness, fatigue
More commonly in proximal muscles
Sensory abnormalities also possible

28. Hyperparathyroid Crisis
Most patents w/ hyperparathyroidism chronically ill w/ renal and skeletal abnormalities
Rarely can become acutely ill
Rapidly developing weakness, N/V, weight loss, fatigue, drowsiness, confusion, Azotemia
Uncontrolled PTH production, hyperCa, polyuria, dehydration, reduced renal function, worsening hyperCa

29. Hyperparathyroid Crisis
Definitive therapy - resection
Must reverse hyperCa first
Diuresis - Saline hydration then Lasix to excrete Ca
Calcitonin - rapid affect, inhibits bone resorption
Steroids - take up to a week
Mithramycin - rapidly inhibiting bone resorption

30. Treatment Only Curative treatment - Parathyroidectomy
Who should have surgery?
Many found incidentally, during routine physicals

31. Who should have surgery?
NIH Consensus statement 1991
All symptomatic
If Assymptomatic
Markedly elevated serum Ca
H/o episode life-threatening hypercalcemia
Reduce renal function
Kidney stone on Radiograph
Markedly elevated urinary Ca excretion
Substantially reduce bone mass

32. Standard Neck Exploration

33. Parathyroidectomy Must find all four glands
Intraoperative frozen section, PTH measurement useful
If single gland enlarged, removal usually curative
If multiple glands enlarged, removed. Normal just biopsied
If all 4 enlarged (generalized parathyroid hyperplasia) - subtotal (3 1/2 removed)
Can reimplant into forearm muscle

34. Superior parathyroid
easier to find
more consistent position
just on dorsal surface of upper thyroid
careful for superior thyroid artery and superior laryngeal nerve

35. Inferior gland
less consistent location
may be near thymus or inside thyroid
careful for recurrent laryngeal nerve betw trachea / esophagus
inferior thyroid artery

37. Success of Surgery May need mediastinoscopy
95% of cases cured at initial neck exploration
If failed intial procedure, can try to localize w/ Radionuclide, detect w/ gamma probe
Sestamibi concentrates in parathyroid tissue
Increasingly used in initial operation
limits dissection
Limits operative time
May need mediastinoscopy